Cancer continues to be a major health problem, despite significant progress made in the area of treatment. The standard treatment regimes of chemotherapy, radiation therapy, surgical intervention and combinations of the three, often fail to produce a long lasting cure. In many cases, the cancer patient having undergone the treatment often relapses back to the disease condition after some period of time, further exacerbating the problem.
Another factor complicating development of a cancer treatment is that cancers have been found to be caused not by a single biological agent or factor, but rather by a combination of agents and factors. Unlike most medical treatments where a single causative agent or event is the focus of the treatment, cancer therapy requires addressing a plurality of biological factors.
In recent years, research has been directed to developing cancer therapies that utilize the patient's own immune system. One such approach is adoptive immunotherapy. Adoptive immunotherapy calls for using the patient's own cells to generate cytotoxic T lymphocytes CTLs) to treat a tumor or cancerous cells.
Since melanoma is known for it's potential to elicit immune responses and is resistant to currently used regimens of systemic treatment, such as chemotherapy and hormone-therapy, most preclinical and clinical studies of immunotherapy regimes target this malignancy. Melanoma is a significant health problem. Over the past four decades the incidence of melanoma has been increasing at a higher rate than any other type of cancer. Although most melanomas are managed by routine surgical excision, for patients with malignant melanoma not amenable to surgical extirpation, treatment options are limited. Dacarbazine remains the drug of choice in disseminated melanoma, but remissions are usually short lived. Interleukin and biochemotherapy have yielded good results but the percentage of patients benefiting this therapy is small. Although high dose interferon increases survival rates in some patients, interferon remains a controversial drug that is not easily tolerated. Sequential chemotherapy has promise, but, current treatment options for individuals suffering from metastatic melanoma are unsatisfactory.
Current immunotherapeutic approaches for treating metastatic melanoma include the administration of melanoma-associated peptides alone, or in combination with exogenous cytokines, gene-modified tumor cells, Dendritic cells loaded with defined peptides or dendritic cells presenting a full complement of antigenic epitopes resulting from internally processed proteins. These approaches attempt to boost T and/or B cell responses in an effort to cure the disease. These approaches remain largely unproven as viable clinical treatment regimes for human patients. Aside from the problem of identifying the proper epitopes with which to immunize the CTL's, the current approaches do not provide for a method of presenting a sufficient number of different epitopes to APCs in order to adequately target multiple antigens to effectively treat the cancer.
The present invention fulfills unmet needs, by providing a cell therapy method for the treatment of tumors. In particular, the present invention relates to a treatment regimen for melanoma using ex vivo-generated autologous T lymphocytes with specificity for melanoma-associated target antigen. Concomitant administration of either IFN-α or IL-2, or both cytokines at specific times and doses can benefit the priming of tumor cells for lysis by the antigen-specific T cells and the in vivo persistence of the CTLs.